4-癌基因与抑癌基因.pptVIP

In normal tissues, proper microRNA (miRNA) transcription, processing and binding to complementary sequences on the target mRNA results in the repression of target-gene expression through a block in protein translation or altered mRNA stability (not shown). The overall result is normal rates of cellular growth, proliferation, differentiation and cell death. b | The reduction or deletion of a miRNA that functions as a tumour suppressor leads to tumour formation. A reduction in or elimination of mature miRNA levels can occur because of defects at any stage of miRNA biogenesis (indicated by question marks) and ultimately leads to the inappropriate expression of the miRNA-target oncoprotein (purple squares). The overall outcome might involve increased proliferation, invasiveness or angiogenesis, decreased levels of apoptosis, or undifferentiated or de-differentiated tissue, ultimately leading to tumour formation. c | The amplification or overexpression of a miRNA that has an oncogenic role would also result in tumour formation. In this situation, increased amounts of a miRNA, which might be produced at inappropriate times or in the wrong tissues, would eliminate the expression of a miRNA-target tumour-suppressor gene (pink) and lead to cancer progression. Increased levels of mature miRNA might occur because of amplification of the miRNA gene, a constitutively active promoter, increased efficiency in miRNA processing or increased stability of the miRNA (indicated by question marks). ORF, open reading frame. * lncRNAs contribute to each of the six hallmarks of cancer (diagram adapted from Hanahan and Weinberg, 2000). Selected examples of lncRNAs and their molecular partners or genomic targets are shown for proliferation, growth suppression, motility, immortality, angiogenesis, and viability cancer phenotypes. * Balmain A, et al Nature Genetics 2003 Summary Inactivation of Tumor Suppressor Gene RB1 PTEN VHL BRCA1/2 APC FBW7 Genetic/Epigenetic Alterations Lead to Cancer